We have obtained blood and tissue from members of 125 high-risk families, each containing three or more confirmed cases of prostate cancer among first-, second-, or third-degree relatives. As of June 1, 1997, we have typed 49 of these families for 162 evenly spaced genomic markers. We also have typed 96 of the families for four markers at the putative hereditary prostate cancer locus 1q24-25. We are contributing the results to a pooled linkage analysis of the region, to be conducted by the International Prostate Cancer Linkage Consortium (IPCLC) established by the US NCI. In addition, by December 31, 1997, we will have gathered epidemiological data, DNA and sera from a population-based sample of 200 white and 150 black men diagnosed with prostate cancer at ages less than 65 years in Northern California during the period 1992-94. We had previously gathered comparable data and biological specimens from 411 white and 315 black men without prostate cancer who served as controls in a population-based case-control study conducted in 1987-91 as part of this project. This competing renewal application requests funds to: 1) to perform linkage/mutation analyses of the 125 high-risk families, to analyze separately and to contribute to the IPCLC; and 2) to evaluate associations of prostate cancer with polymorphisms of the androgen receptor (AR) and the vitamin D receptor (VDR) genes. These data offer the opportunity to examine whether associations noted in other case-control studies are seen also in families, who provide control for potential confounding due to population stratification of alleles, and in blacks, who are at high risk of prostate cancer. The data also offer the opportunity to: a) evaluate black/white differences in prevalence of high-risk alleles and use the results to estimate the proportion of prostate cancer in each race attributable to the polymorphisms, and b) estimate the proportion of black/white differences in risk that might be explained by racial differences in prevalence of the high-risk alleles, if the associations were causal.